The Impact of CYP2C19 Genotype on the Platelet Reactivity Index (PRI) among Chronic Coronary Syndromes (CCS) Patients Undergoing Percutaneous Coronary Intervention (PCI): Affectability of Rapid Genetic Testing.

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Drugs and Therapy Pub Date : 2025-04-01 Epub Date: 2024-01-15 DOI:10.1007/s10557-024-07544-6

Mohammed Ahmed Akkaif, Nur Aizati Athirah Daud, Dzul Azri Mohamed Noor, Abubakar Sha'aban, Muhamad Ali Sk Abdul Kader, Baharudin Ibrahim

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引用次数: 0

Abstract

Background: In the Asian population, the presence of the CYP2C19 loss-of-function (LOF) allele is a known genetic variation. This allele is associated with a reduced capacity to metabolize clopidogrel into its active forms through the CYP2C19 enzyme, resulting in diminished platelet inhibition and an elevated risk of recurrent cardiovascular events. Regulatory authorities have recommended an alternative P2Y12 inhibitor, ticagrelor, for individuals carrying the LOF allele. Consequently, this study seeks to assess the impact of the CYP2C19 genotype on the Platelet reactivity index (PRI) using a rapid genetic testing approach in Asian patients with chronic coronary syndromes (CCS) who undergo percutaneous coronary intervention (PCI).

Methods: This prospective study employed a parallel design, single-center design, and randomized approach. Genotyping for the CYP2C19*2 and *3 polymorphisms was conducted using the Nested Allele-Specific Multiplex PCR (NASM-PCR) technique. Patients meeting the inclusion criteria underwent genotyping for CYP2C19 polymorphisms. Following PCI, patients were randomly assigned to receive either ticagrelor or clopidogrel. PRI assessments were performed four hours after loading dose administration. The trial was registered with ClinicalTrials.gov under the identifier NCT05516784.

Results: Among the 94 patients recruited for the study, 40 (42.55%) were identified as carriers of the LOF allele for CYP2C19*2 and *3 (*1/*2, *2/*2, *1/*3). Out of the 84 patients evaluated for PRI (44 receiving clopidogrel and 40 receiving ticagrelor), 21 (47.7%) of the clopidogrel group and 39 (97.5%) of the ticagrelor group exhibited a favorable response to antiplatelet therapy (PRI < 50). Patients treated with ticagrelor demonstrated superior antiplatelet responses compared to those receiving clopidogrel, regardless of LOF carrier status (P = 0.005 and < 0.001 for non-LOF and LOF carriers, respectively).

Conclusion: NASM-PCR as a rapid genetic test holds promise for personalizing antiplatelet therapy in Asian CCS patients.

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接受经皮冠状动脉介入治疗 (PCI) 的慢性冠状动脉综合征 (CCS) 患者的 CYP2C19 基因型对血小板反应性指数 (PRI) 的影响：快速基因检测的影响。

背景：在亚洲人群中，CYP2C19 功能缺失（LOF）等位基因的存在是一种已知的遗传变异。该等位基因与通过 CYP2C19 酶将氯吡格雷代谢为活性形式的能力降低有关，从而导致血小板抑制作用减弱和复发性心血管事件风险升高。监管机构建议携带 LOF 等位基因的患者使用另一种 P2Y12 抑制剂替卡格雷。因此，本研究试图采用快速基因检测方法，在接受经皮冠状动脉介入治疗（PCI）的亚洲慢性冠状动脉综合征（CCS）患者中评估 CYP2C19 基因型对血小板反应性指数（PRI）的影响：这项前瞻性研究采用平行设计、单中心设计和随机方法。采用巢式等位基因特异性多重 PCR（NASM-PCR）技术对 CYP2C19*2 和 *3 多态性进行基因分型。符合纳入标准的患者接受了 CYP2C19 多态性基因分型。PCI后，患者被随机分配接受替卡格雷或氯吡格雷治疗。给药四小时后进行PRI评估。该试验已在 ClinicalTrials.gov 注册，标识符为 NCT05516784：在被招募参加研究的 94 名患者中，有 40 人（42.55%）被确定为 CYP2C19*2 和 *3 的 LOF 等位基因（*1/*2、*2/*2、*1/*3）携带者。在接受 PRI 评估的 84 例患者（44 例接受氯吡格雷治疗，40 例接受替卡格雷治疗）中，氯吡格雷组的 21 例（47.7%）和替卡格雷组的 39 例（97.5%）表现出对抗血小板治疗的良好反应（PRI 结论）：作为一种快速基因检测方法，NASM-PCR有望为亚洲慢性阻塞性肺病患者提供个性化的抗血小板治疗。

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来源期刊

Cardiovascular Drugs and Therapy 医学-心血管系统

CiteScore

8.30

自引率

0.00%

发文量

110

审稿时长

4.5 months

期刊介绍： Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.